The major goals of the proposal are (1) to determine the usefulness of antimitotic, anti-inflammatory and connective tissue inhibiting drugs in the prevention of atheromatous plaque formation and management of atherosclerosis and coronary heart disease and (2) to elucidate the role of connective tissue and arterial smooth muscle cells in the pathogenesis of these diseases. The potential use and mode of action of these agents in atherosclerosis will be evaluated in the rabbit and in the macaca irus monkey. The morphological changes in the arteries will be correlated with the biochemical and metabolic changes in the lipids and connective tissue proteins contained in the arteries (elastin, collagen, glycoproteins and mucopolysaccharides). Recent studies in rabbits suggest that certain antiproliferative and anti-inflammatory drugs which have specific inhibitory effects on the atherosclerotic process could prove to be useful in the control of atherosclerosis and its sequelae.